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Sterility Assurance Level (SAL) - A Quick Intro
Invasive Medical Devices are never fully “sterilized”,
however you can control the level of sterility based on your product’s bioburden
and sterilization.
When a product is sterilized, either by Ethylene Oxide or gamma radiation cycles
(or other methods), the level of sterilization never guarantees that the product
will be completely sterile. One reason for this is that the sterilization method
works by reducing the number of viable microorganisms logarithmically.
Several factors result in the ultimate level of living organisms on medical
devices following sterilization. The two factors that are usually at work are
the number of microorganisms that sit on your product (known as bioburden) and
the amount of sterilization that is applied.
BIOBURDEN (WHERE IT ALL BEGINS)
When a product is manufactured a number of microorganisms are introduced.
Depending on the circumstances, such as whether or not a clean room is used, the
level or degree of contamination will vary.
It is highly recommended that a medical device manufacturer of invasive or
mucous or blood contacting devices, adopt a bioburden program early in
development. Controlling the types and quantity of organisms coming into contact
with your device results in controlling and demonstrating the level of sterility
of that device. It is for this reason many manufacturers have put in place clean
rooms with varying classifications for the manufacturing of their devices.
A good bioburden program can be demonstrated using metrics. Some manufacturers
have adopted Statistical Process Control (SPC) techniques for quantifying the
number of microorganisms introduced to their products during the manufacturing
process. Over time those using SPC can show if their process is in control and
whether any anomalies have been introduced into that process. Anomalies or
spikes in the process can be an indication that something has gone wrong. An
unusual spike in the amount of bioburden should result in a nonconformance and
subsequent investigation.
In addition to the numbers of microorganisms it is equality important to
determine the types of microorganisms that are present.
You can submit a number of unprocessed units to a good laboratory to quantify
and determine the types of microorganisms present on pre-sterilized products.
The frequency of determining bioburden is based on the method of sterilization
that you decide to use however it is recommended that at you do this at least
monthly or more often. Especially if an out-of-control situation (unusual spike)
occurs.
STERILIZATION
Sterilization can occur by various methods. Depending on the nature of the
design, material and/or packaging some methods have advantages over others. In
all cases the level of sterilization is based on the pre-sterilized bioburden.
In some cases the bioburden should influence the sterilization method. For
instance there is some cotton that should be sterilized by steam due to the
presence of a fungus known as Pyronema domesticum.
When the sterilization method is chosen the method requires validation. The
validation method is based on determining the Sterility Assurance Level (SAL).
The sterility assurance level can vary depending on the application of the
device and is set by various standards and requirements. For invasive products
the level is usually 10-6 or 1 in a million. The number 10-6 denotes the number
of products that will have a living microorganism following the sterilization
process. In other words, once the sterilization is completed the odds of finding
an unsterile product will be 1 in a million. As indicated some products are
adequate with having a SAL of only 1 in a thousand.
HOW IS SAL DETERMINED?
To explain the way SAL is determined this article will use the example of
Ethylene Oxide sterilization.
Let’s say you have a product (like an artificial hip) that requires
sterilization. You may start off with a few thousand units – each individually
packaged to ensure that the product remains sterile following the process.
Depending on the number of products you validate for your sterilization cycle
you will have a certain number. In many cases the products will be sent to the
manufacturer on pallets (or skids). Each pallet will have a number of cases
which are placed on the pallet to a specific configuration.
In the case of Ethylene Oxide sterilization the method for validating the
sterilization process can follow ISO 13485 or EN 550. These standards require
that a number of Biological Indicators (BI) be placed within the product in an
orientation that is deemed “worst case scenario”. Many manufacturers will
validate using product that has been seeded with the microorganism that is used
in the Biological Indicators. For Ethylene Oxide sterilization the bacterium
used is bacillus subtilis.
Bacillus subtilis is a microorganism that is know to be very resistant to
ethylene oxide sterilization. Why use it? Because you hope that the organism
will be more resistant than the worst types of microorganisms that live on you
product. Hence this is one of the reason why you would want to know the types of
microorganisms on your product.
The amount of bacillus subtilis on each BI will be in the range of 106 but never
less than one million. The actual number of organisms on each lot of Biological
Indicators should be validated by sending them to laboratory. The lab will
enumerate them and send you a certificate. There are a number of reasons you
should not count on the certificate that is issued by the BI manufacturer alone.
One is that of control. Biological Indicators should be controlled and stored in
temperature/humidity environment that is recommended by the manufacturer. This
environment should be monitored to ensure compliance. Out-of-specification
changes in environment should result in a new enumeration by an accredited
laboratory.
HALF CYCLE
During sterilization validation - for Ethylene Oxide sterilization, the product
is introduced into a chamber and then exposed to half the anticipated
sterilization cycle. The biological indicators are retrieved and then evaluated
for complete sterility. If you will recall the sterilization process occurs
logarithmically. If all the biological indicators result in no growth it is
assumed that the process had subjected the product to a sterility effectiveness
to reduce the roughly 1 million bacteria to 100 or 1. You would be expected to
see one BI fail if you start off with a million BI strips (which is never the
case).
But you are not finished. Remember that FDA and other requirements require
specific SALs. For invasive products you would be expected to have an SAL of at
least 10-6. To ensure that your products have an SAL of at least 10-6 you need
to take into consideration the number of microorganisms that will be expected to
be introduced to your product, hence the importance of conducting regular
Bioburden testing.
If your product – let’s say usually as 102 or 100 microorganisms living on the
product – the best you can prove the half cycle sterilization has given you is
10-4. To ensure an SAL of at least 10-6 a method is used in Ethylene Oxide
sterilization (which is referred to the overkill method) by doubling the length
of the Half cycle. By doubling the time for sterilization exposure for routine
processing you in effect impart a sterilization effectiveness of 10-12. Hence if
you begin with 100 or 1000 microorganisms per device you will always be assured
to have product that meets an SAL of at least 10-6.
CONCLUSION
Establishing a good bioburden program and controlled manufacturing process is
the first step in being able to demonstrate that your products are meeting a
required SAL. In all cases you should consult with your sterilization provider
and/or laboratory used for evaluating your devices and biological indicators on
ways to improve assurance.
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